One of the principal objectives of this proposal is to determine the origin and describe the differentiation processes involved in the formation of mucus secreting cells in the trachea epoithelium. It is now generally accepted that the mechanisms controlling the differentiation of precursor cells to fully functional mucus-secreting cells depend on the ability of various stimuli to induce and increase the rate of synthesis and secretion of mucin glycoproteins. Hormones, allergens and other stimulatory factors may exert their effects, in part, by stimulating the differentiation of precursor cells in the basal layer to goblet cells in the epithelium. Our approach to further knowledge on the regulation of glycoprotein biosynthesis in this tissue will be to carefully characterize individual cell types in this tissue and then study their transformation to mucus-secreting cells. The use of isolated cell systems represents a definitive and precise approach to the study of the complex processes responsible for the regulation of trachea mucin glycoprotein synthesis. A denuded trachea organ culture system will also be used to study this differentiation process under conditions mimicking hypersecretion of mucus. The influence of various irritants on the differentiation process as monitored by the rate of synthesis of acidic mucin glycoproteins will be studied with this trachea explant system. An understanding of the growth, regulatory properties and interconversions of various cell types in the tracheal mucosa is fundamental to understanding the mechanisms which regulate the synthesis and secretion of mucin glycoprotein in respiratory tissues.